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Our immune system is exceptionally powerful. It rapidly mobilizes teams of cells to eliminate threats within our bodies. But sometimes, it hits the wrong target. Autoimmune diseases such as lupus and multiple sclerosis result from friendly fire — immune cells mistakenly attacking healthy tissues and organs. New treatments and therapeutic targets for these conditions are urgently needed.

Now, Cold Spring Harbor Laboratory (CSHL) professor Christopher Wacock may have stumbled upon a new therapeutic target — hiding in plain sight. Vakoc and his team discovered that IκBζ, a well-studied protein in the field of immunology, contains an overlooked sequence, which allows it to activate key proteins in immune cells. While the sequence — the OCA peptide — is small, targeting it can have significant effects in the destruction of immune cells.

For years, IκBζ was known to have an important function — regulating NFκB, a protein important for mounting immune responses. But it turns out that IκBζ has dual functions. Vakok’s team found that it also activates another important family of immune proteins called POUs. And it does this through the OCA peptide. Disarming both immune responses can ensure the fastest response to threats — a hallmark of our natural defenses.

“The immune system, for example, falls over most of the time,” says Vakok. “But the moment a pathogen arrives, it needs to adapt very quickly.” The ability to respond within seconds is critical to eradicating bacteria, invading viruses, or even cancer. Time is of the essence.”

Why has evolution assigned this lunar function to IκBζ? Vakok suspects it has something to do with many of the immune system’s functions. While immune cells activate many of the same proteins, each cell also has its own functions. Medicine of IκBζ can give our body’s defenses the ability to rapidly switch between roles.

“Evolution often involves finding creative and efficient solutions to problems in life,” Vakuk explains. “We believe that the OCA peptide allows different types of immune cells to respond rapidly with the right genes at the right time and place. It’s all about personalizing the immune response for different cells in the body. “

This discovery may form the basis of immunotherapy against autoimmune diseases in the future. Because the OCA peptide is well characterized and found in many immune cells, it may make an important drug target. And that’s where Wacok will set his sights next.

“Targeting IκBζ with this OCA peptide will have interesting effects on the immune system, with highly cell-type-specific effects,” says Wakok. “Our future research will explore this question.”

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